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The absence of standardized protocols for integrating end-stage renal disease patient data into AI models has constrained the potential of AI in enhancing patient care. Here, we present a protocol for processing electronic medical records from 1,336 peritoneal dialysis patients with more than 10,000 follow-up records. We describe steps for environment setup and transforming records into analyzable formats. We then detail procedures for developing a directly usable dataset for training AI models to predict one-year all-cause mortality risk. For complete details on the use and execution of this protocol, please refer to Ma et al.1.
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Several interventional studies have revealed the beneficial impact of curcumin supplementation on blood pressure and endothelial function, but the findings are conflicting. Therefore, this study was conducted to investigate the effects of curcumin supplementation on blood pressure and endothelial function. A meta-analyses of randomized clinical trials were performed by searching PubMed, Embase, Scopus, and Web of Science were searched up to March 31, 2024. Random effects models were used to calculate weighted mean differences (WMD). Pooled estimates of 10 studies revealed that curcumin decreased diastolic blood pressure (DBP) [WMD = -0.94, 95â¯% CI: -1.59, -0.30; p = 0.004], pulse wave velocity (PWV) [WMD = -45.60, 95â¯% CI: -88.16, -3.04; p = 0.03, I2 = 0.0â¯%, p = 0.59], and vascular cell adhesion molecule-1 (VCAM-1) [WMD = -39.19; 95â¯% CI: -66.15, -12.23, p =0.004; I2=73.0â¯%, p =â¯0.005] significantly, and increased flow-mediated dilation (FMD) [WMD = 1.64, 95â¯% CI: 1.06, 2.22; p <â¯0.001, I2 = 0.0â¯%, p = 0.61. However, curcumin did not significantly change systolic blood pressure (SBP) [WMD = -0.64, 95â¯% CI: -1.96, 0.67; p =0.34, I2 = 83.5â¯%, p <0.001], and Intercellular Adhesion Molecule 1 (ICAM1) [WMD = -17.05; 95â¯% CI: -80.79, 46.70, p =0.601; I2=94.1â¯%, p <â¯0.001]. These results suggest that curcumin has a beneficial effect on DBP, PWV, VCAM-1 and FMD levels and may be an effective adjunctive therapy for improving blood pressure and endothelial function.
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Dicentrinone (Di), liriodenine (Li) and lysicamine (Ly) are three natural oxoaporphine alkaloids (OAs), which revealed significant biological activity such as anticancer, anti-inflammatory and antimicrobial activities and were considered as potential lead compounds for the development of new clinical chemicals. In the present study, confocal laser scanning fluorescence microscopy observation demonstrated these three natural OAs could traverse inside of the nucleus and get an opportunity to interact with DNA. Their interaction properties with DNA were then investigated simultaneously by two spectral fluorescent probes of ethidium bromide (EB) and methyl green (MG), as well as UV-vis absorption and cyclic voltammetry measurements, and further verified by the molecular docking analysis. Results indicated Di and Li were distinctly classified as the intercalative molecules to DNA, however, Ly was confirmed with a mixed-mode binding of partial intercalation and groove affinity. Their binding ability was revealed as the follows: Di ≥ Li > Ly, which was correlated with their structural changes. Thermodynamic studies revealed the binding process of Li and Ly with ctDNA was all spontaneous, the hydrophobic interaction was the major binding force for Li-ctDNA complex, however, the interaction between Ly and ctDNA relied on both hydrophobic and hydrogen binding force. Molecular docking provided detailed computational interaction of Di, Li and Ly with DNA, which proved the intercalation binding of Li-DNA complex and Di-DNA complex stabilizing mainly by the π-π binding force, however, apart from a small quantity of π-π interaction, another binding force in the Ly-DNA complex mainly was supplied from the weaker Pi-Alkyl, hydrogen bond and Pi-Anion interactions.
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BACKGROUND: Although colistin is widely recognized as the last line of antibiotics against gram-negative bacteria, the emergence and spread of colistin resistance severely diminish its clinical efficacy and application. An alternative strategy to alleviate this crisis is to identify promising colistin adjuvants with enhanced antibacterial activity. PURPOSE: In this study, the adjuvant effects of paeonol on colistin and the underlying mechanisms were investigated. METHOD: Minimum Inhibitory Concentration (MIC) and checkerboard assays were used to investigate the adjuvant activity and structure-activity relationship of paeonol on the antibacterial effect of colistin in vitro. Time-dependent killing and resistance development assays were used to investigate the bactericidal effects and emergence of colistin resistance. Different fluorescent probes and competitive inhibition tests were used to investigate bacterial membrane functions and potential targets. Skin infection and peritonitis-sepsis models were used to evaluate the combined in vivo effects of colistin and paeonol in vivo. RESULT: Paeonol enhanced the antibacterial effects of colistin against gram-negative bacteria, particularly Klebsiella pneumoniae. Structure-activity relationship analysis showed that the hydroxyl, 4-methoxy and ketone carbonyl side chains of the benzene ring contributed to the adjuvant effect of paeonol. Paeonol enhances the bactericidal effects of colistin and minimizes the emergence of colistin resistance. Notably, mechanistic studies demonstrated that the combination of colistin and paeonol enhances membrane disruption and oxidative damage, possibly via interactions with phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CAL). Importantly, paeonol enhanced the efficacy of colistin in both the skin and peritonitis infection models. CONCLUSION: This is the first report on the adjuvant potential of paeonol in colistin to combat K. pneumoniae by promoting membrane disruption and oxidative damage via targeting membrane phospholipids. Notably, the verified target, PE, provides an additional avenue for screening new colistin adjuvants.The combination therapy of paeonol and colistin is a promising strategy for treating infections caused by gram-negative pathogens to address antibiotic resistance issues.
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OBJECTIVE: This paper aims to evaluate the literature on the prevalence of psychological distress and its associated factors in patients with breast cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure and Wanfang were searched from inception to 11 June 2024. ELIGIBILITY CRITERIA: Studies reported data on the prevalence and correlates of psychological distress were included. Review, letter, conference abstracts and articles not available in English and Chinese were excluded. DATA EXTRACTION AND SYNTHESIS: Two researchers independently conducted literature screening, data extraction and bias risk assessment. Meta-analysis was employed to estimate the prevalence and correlates of psychological distress in patients with breast cancer. The Agency for Healthcare Research and Quality and the Newcastle-Ottawa Scale were used for quality assessment. Meta-analysis was performed by using the R V.4.1.1 software. RESULTS: In total, 34 studies representing 13 828 patients with breast cancer were included in the study. Most of the studies were cross-sectional study (n=25, 73.53%%). The pooled prevalence of psychological distress was 50% (95% CI 42% to 58%, I2=98%). Results showed that psychological distress was positively correlated with younger age (z=0.13, 95% CI 0.07 to 0.20), having children (z=0.39, 95% CI 0.11 to 0.61), poor financial situation (z=0.12, 95% CI -0.03 to 0.26), short time since diagnosis (z=0.19, 95% CI 0.01 to 0.36), previous treatment (z=0.15, 95% CI 0.03 to 0.27), distant metastasis (z=0.31, 95% CI 0.07 to 0.52), chemotherapy (z=0.22, 95% CI 0.05 to 0.38), prior emotional status (z=0.40, 95% CI 0.29 to 0.50), body image damaged (z=0.10, 95% CI -0.01 to 0.21), negative coping (z=0.12, 95% CI -0.11 to 0.34), communication avoidance (z=0.32, 95% CI 0.24 to 0.39) and negatively correlated with married (z=-0.25, 95% CI 0.45 to -0.02), high education level (z=-0.19, 95% CI -0.40 to 0.05), having insured (z=-0.04, 95% CI -0.15 to 0.08), full employment (z=-0.40, 95% CI -0.61 to -0.14), time of completion of treatment (z=-0.12, 95% CI -0.30 to -0.06), surgery (z=-0.05, 95% CI -0.53 to 0.45), social support (z=-0.18, 95% CI -0.29 to -0.06), post-traumatic growth (z=-0.19, 95% CI -0.34 to -0.03), good physical conditions (z=-0.17, 95% CI -0.29 to -0.04), positive coping (z=-0.22, 95% CI -0.53 to 0.15). CONCLUSION: Our findings indicated that the prevalence of psychological distress in patients with breast cancers was 50% and 21 correlates of psychological distress. Screening and evidence-based interventions are urgent and essential to address this public concern and promote the health of patients with breast cancer. PROSPERO REGISTRATION NUMBER: CRD42023397109.
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Neoplasias da Mama , Angústia Psicológica , Humanos , Neoplasias da Mama/psicologia , Neoplasias da Mama/epidemiologia , Feminino , Prevalência , Estresse Psicológico/epidemiologia , Fatores de RiscoRESUMO
[Background] Intercropping is considered an effective approach to defending rice disease. [Objectives/Methods] This study aimed to explore the resistance mechanism of rice intraspecific intercropping by investigating soil metabolites and their regulation on the rhizosphere soil microbial community using metabolomic and microbiome analyses. [Results] The results showed that the panicle blast disease occurrence of the resistant variety Shanyou63 (SY63) and the susceptible variety Huangkenuo (HKN) were both decreased in the intercropping compared to monoculture. Notably, HKN in the intercropping system exhibited significantly decreased disease incidence and increased disease resistance-related enzyme protease activity. KEGG annotation from soil metabolomics analysis revealed that phenylalanine metabolic pathway, phenylalanine, tyrosine, and tryptophan biosynthesis pathway, and fructose and mannose metabolic pathway were the key pathways related to rice disease resistance. Soil microbiome analysis indicated that the bacterial genera Nocardioides, Marmoricola, Luedemannella, and Desulfomonile were significantly enriched in HKN after intercropping, while SY63 experienced a substantial accumulation of Ruminiclostridium and Cellulomonas. Omics-based correlation analysis highlighted that the community assembly of Cellulomonas and Desulfomonile significantly affected the content of the metabolites D-sorbitol, D-mannitol, quinic acid, which further proved that quinic acid had a significantly inhibitory effect on the mycelium growth of Magnaporthe oryzae, and these three metabolites had a significant blast control effect. The optimal rice blast-control efficiency on HKN was 51.72%, and Lijiangxintuanheigu (LTH) was 64.57%. [Conclusions] These findings provide a theoretical basis for rice varieties intercropping and sustainable rice production, emphasizing the novelty of the study in elucidating the underlying mechanisms of intercropping-mediated disease resistance.
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INTRODUCTION: Different initial manifestations of peritoneal dialysis-associated peritonitis (PDAP) may depend on the type of pathogenic organism. We investigated the association between the clinical characteristics of PDAP and susceptibility to vancomycin and investigated the possibility of using vancomycin monotherapy alone as an initial treatment regimen for some PDAP patients to avoid unnecessary antibiotic exposure and secondary infection. METHODS: Patients with culture-positive PDAP were retrospectively analyzed and divided into two groups: peritonitis with only cloudy effluent (PDAP-cloudy) or with cloudy effluent, abdominal pain and/or fever (PDAP-multi). The bacterial culture of PD effluent and antibiotic sensitivity test results were compared between groups. Logistic regression was used to investigate factors predicting susceptibility to vancomycin. RESULTS: Of 162 episodes of peritonitis which had a positive bacterial culture of PD fluid, 30 peritonitis were in the PDAP-cloudy group, and 132 peritonitis were in the PDAP-multi group. Thirty (100%) peritonitis in the PDAP-cloudy group had gram-positive bacterial infections, which was significantly greater than that in the PDAP-multi group (51.5%) (P < 0.001). Twenty-nine (96.7%) peritonitis in the PDAP-cloudy group were susceptible to vancomycin, compared to 67 (50.8%) in the PDAP-multi group (P < 0.001). The specificity of PDAP-cloudy for vancomycin-sensitive peritonitis was 98.48%. Only one patient (3.3%) in the PDAP-cloudy group experienced vancomycin-resistant peritonitis caused by Enterococcus gallinarum, which could neither be covered by vancomycin nor by the initial antibiotic regimen recommended by the current ISPD guidelines. The presence of only cloudy effluent was an independent predictor of susceptibility to vancomycin according to multivariate analysis (OR = 27.678, 95% CI 3.191-240.103, p = 0.003), in addition to PD effluent WBC counts (OR = 0.988, 95% CI 0.980-0.996, p = 0.004), diabetes mellitus (OR = 3.646, 95% CI 1.580-8.416, p = 0.002), first episode peritonitis (OR = 0.447, 95% CI 0.207-0.962, p = 0.039) and residual renal creatinine clearance (OR = 0.956, 95% CI 0.918-0.995, p = 0.027). Addition of these characteristics increased the AUC to 0.813 (95% CI 0.0.749-0.878, P < 0.001). The specificity of presenting with only cloudy effluent for vancomycin-sensitive peritonitis was 98.48%. CONCLUSIONS: Cloudy dialysate, as the only symptom at PDAP onset, was an independent predictor of vancomycin-sensitive PDAP, which is an important new insight that may guide the choice of initial antibiotic treatment.
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Antibacterianos , Diálise Peritoneal , Peritonite , Vancomicina , Humanos , Peritonite/microbiologia , Peritonite/tratamento farmacológico , Peritonite/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Estudos Retrospectivos , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Idoso , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Testes de Sensibilidade Microbiana , AdultoRESUMO
AIM: To investigate the impact of public health emergencies on the prevalence of suicidal ideation among healthcare workers (HCWs) and medical students. METHODS: The prevalence of suicidal ideation among HCWs and medical students was searched for analysis. The platforms included PubMed, medRVix, bioRvix, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Interrupted time-series analysis was employed to determine whether the COVID-19 pandemic influenced the prevalence and trends of suicidal ideation. To account for autocorrelation and heteroskedasticity, Newey-West standard errors were utilized with a lag of order one. RESULTS: Seventy studies with 145,641 HCWs and medical students from 30 countries were included in the final analysis, with 30 studies before COVID-19 and 40 studies during the pandemic. Before the pandemic outbreak (April 2020), the monthly increasing rate was 0.063 % (95 % CI: -0.009 %, 0.135 %, z = 1.73, P = 0.084). The tendency of suicidal ideation prevalence increased by 1.116 % (95%CI: 0.888 %, 1.344 %, z = 9.60, P < 0.001). In other words, the calculated monthly growth rate of suicidal ideation after the pandemic outbreak is 1.179 % (95%CI: 0.968 %, 1.391 %, z = 10.93, P < 0.001) per month. The overall growing trend of prevalence of suicidal ideation during the pandemic is 1.896 % per month in America; 1.590 % in Europe; 0.443 % (95%CI: 0.213 %, 0.673 %, z = 3.77, P < 0.001) in Asia; 1.055 % in HCWs; and 0.645 % in medical students. CONCLUSION: This study highlights that the COVID-19 pandemic can significantly impact the prevalence of suicidal ideation among HCWs and medical students, and the prevalence showed an upward trend.
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The expression pattern of GLOD4 in the testis and its regulatory effect on testicular cells was explored in goats to enhance our understanding of spermatogenesis and improve reproduction in breeding rams. In this study, we demonstrated the localization of GLOD4 in testicular cells using immunohistochemistry and subcellular localization analyses. Subsequently, we analyzed the GLOD4 expression pattern in four age-based groups (0, 6, 12, and 18 months old) using real-time quantitative polymerase chain reaction (qRT-PCR) and protein blotting. Finally, we performed GLOD4 silencing and overexpression studies in Leydig cells (LCs) and explored the effects on cell proliferation, the cell cycle, steroid hormone secretion and the expression of candidate testosterone hormone-regulated genes. GLOD4 was mainly expressed in Leydig cells, and the subcellular localization results showed that the GLOD4 protein was mainly localized in the cytoplasm and nucleus. Silencing of GLOD4 significantly suppressed the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3ß-HSD, and CYP17A1 and the mRNA expression levels of cell cycle-related genes CDK6, PCNA, and Cyclin E. Moreover, the cell cycle was blocked at the G2/M phase after GLOD4 silencing, which significantly suppressed testosterone secretion. In contrast, GLOD4 overexpression significantly increased the mRNA expression levels of the testosterone secretion-related genes CYP11A1, 3ß-HSD, and CYP17A1 and increased the expression of the cell cycle-related genes CDK6, PCNA, and Cyclin E. Moreover, GLOD4 overexpression promoted the cell cycle from G0/G1 phases to enter the S phase and G2/M phases, promoted the secretion of testosterone. Taken together, our experimental results indicate that GLOD4 may affect the development of cells in Qianbei Ma goats of different ages by influencing the cell cycle, cell proliferation, and testosterone hormone synthesis. These findings enhance our understanding of the functions of GLOD4 in goats.
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BACKGROUND: There were limited data investigating platelet indices in predicting peritoneal dialysis (PD) outcomes on comorbidities. The aim of this study was to evaluate the association between platelet indices and new-onset comorbidity and all-cause mortality in PD patients. METHODS: A single-center, retrospective observational cohort study was conducted in incident PD patients from 28 December 2011 to 24 January 2018, and followed up until 31 December 2022. Time to the first new-onset cardiovascular disease (CVD) and time to the first new-onset infection event after PD were identified as the primary outcomes. All-cause mortality was identified as the secondary endpoint. The correlation between platelet indices and comorbidities and all-cause mortality were assessed by Cox model. Data of liver disease status was not collected and analyzed. Survival curves were performed by Kaplan-Meier method with log-rank tests. RESULTS: A total of 250 incident PD patients with a median follow-up of 6.79 (inter-quarter range 4.05, 8.89) years was included. A total of 81 and 139 patients experienced the first new-onset CVD and infection event respectively during the follow-up period. High mean platelet volume (MPV) was independently associated with high risk of time to the first new-onset CVD (HR 1.895, 95% CI 1.174-3.058, p = 0.009) and all-cause mortality (HR 1.710, 95% CI 1.155-2.531, p = 0.007). Patients with low mean platelet volume to platelet count ratio (MPV/PC) were prone to occur the new-onset infection events (log rank 5.693, p = 0.017). Low MPV/PC (HR 0.652, 95% CI 0.459-0.924, p = 0.016) was significantly associated with the time to the first new-onset infection event on PD. CONCLUSIONS: Platelet indices were associated with the new-onset CVD, infectious comorbidities and all-cause mortality on PD. Low MPV/PC was associated with time to the first new-onset infection event in PD patients. Moreover, high MPV was associated with new-onset CVD and all-cause mortality in the incident PD patients.
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Doenças Cardiovasculares , Comorbidade , Volume Plaquetário Médio , Diálise Peritoneal , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Estudos de Coortes , Idoso , Plaquetas , Adulto , Contagem de Plaquetas , Infecções/mortalidade , Infecções/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidadeRESUMO
Retinal injury may be exacerbated by iron overload. Astragaloside IV (AS-IV) has potential applications in the food and healthcare industry to promote eye health. We sought to determine the mechanisms responsible for the protective effects of AS-IV on photoreceptor and retinal pigment epithelium cell death induced by iron overload. We conducted in vitro and in vivo experiments involving AS-IV pretreatment. We tested AS-IV for its ability to protect iron-overload mice from retinal injury. In particular, we analyzed the effects of AS-IV on iron overload-induced ferroptosis in 661W and ARPE-19 cells. AS-IV not only attenuated iron deposition and retinal injury in iron-overload mice but also effectively reduced iron overload-induced ferroptotic cell death in 661W and ARPE-19 cells. AS-IV effectively prevented ferroptosis by inhibiting iron accumulation and lipid peroxidation. In addition, inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) eliminated the protective effect of AS-IV against ferroptosis. The results suggest that ferroptosis might be a significant cause of retinal cell death associated with iron overload. AS-IV provides protection from iron overload-induced ferroptosis, partly by activating the Nrf2 signaling pathway.
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Ferroptose , Sobrecarga de Ferro , Camundongos Endogâmicos C57BL , Epitélio Pigmentado da Retina , Saponinas , Triterpenos , Ferroptose/efeitos dos fármacos , Animais , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Saponinas/farmacologia , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/tratamento farmacológico , Camundongos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Humanos , Doenças Retinianas/prevenção & controle , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Doenças Retinianas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Western Blotting , Masculino , Ferro/metabolismoRESUMO
The bidirectional regulation between the gut microbiota and brain, known as gut-brain axis, has received significant attention. The myelin sheath, produced by oligodendrocytes or Schwann cells, is essential for efficient nervous signal transmission and the maintenance of brain function. Growing evidence shows that both oligodendrogenesis and myelination are modulated by gut microbiota and its metabolites, and when dysbiosis occurs, changes in the microbiota composition and/or associated metabolites may impact developmental myelination and the occurrence of neurodevelopmental disabilities. Although the link between the microbiota and demyelinating disease such as multiple sclerosis has been extensively studied, our knowledge about the role of the microbiota in other myelin-related disorders, such as neurodegenerative diseases, is limited. Mechanistically, the microbiota-oligodendrocyte axis is primarily mediated by factors such as inflammation, the vagus nerve, endocrine hormones, and microbiota metabolites as evidenced by metagenomics, metabolomics, vagotomy, and morphological and molecular approaches. Treatments targeting this axis include probiotics, prebiotics, microbial metabolites, herbal bioactive compounds, and specific dietary management. In addition to the commonly used approaches, viral vector-mediated tracing and gene manipulation, integrated multiomics and multicenter clinical trials will greatly promote the mechanistic and interventional studies and ultimately, the development of new preventive and therapeutic strategies against gut-oligodendrocyte axis-mediated brain impairments. Interestingly, recent findings showed that microbiota dysbiosis can be induced by hippocampal myelin damage and is reversible by myelin-targeted drugs, which provides new insights into understanding how hippocampus-based functional impairment (such as in neurodegenerative Alzheimer's disease) regulates the peripheral homeostasis of microbiota and associated systemic disorders.
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Eixo Encéfalo-Intestino , Doenças Desmielinizantes , Microbioma Gastrointestinal , Homeostase , Oligodendroglia , Microbioma Gastrointestinal/fisiologia , Humanos , Animais , Oligodendroglia/metabolismo , Homeostase/fisiologia , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/microbiologia , Eixo Encéfalo-Intestino/fisiologia , Disbiose/microbiologia , Bainha de Mielina/metabolismoRESUMO
Cancer presents a significant health threat, necessitating the development of more precise, efficient, and less damaging treatment approaches. To address this challenge, we employed the 1-ethyl-(3-dimethyl aminopropyl) carbodiimide/N-hydroxy succinimide (EDC/NHS) catalytic system and utilized quaternized chitosan oligosaccharide (HTCOSC) as a drug carrier to construct a nanoparticle delivery system termed HTCOSC-cRGD-ES2-MTX (CREM). This system specifically targets integrin αvß3 on tumor cell surfaces and enables simultaneous loading of the antiangiogenic agent ES2 (IVRRADRAAVP) and the chemotherapy drug methotrexate (MTX). Due to its amphiphilic properties, CREM self-assembles into nanoparticles in aqueous solution, exhibiting an average diameter of 179.47 nm. Comparative studies demonstrated that CREM, in contrast to free ES2 and MTX-free nanoparticles (CRE), significantly suppressed the proliferation of EAhy926 endothelial cells and B16 melanoma cells in vitro, resulting in inhibition rates of 71.18 and 82.25%, respectively. Furthermore, CREM exhibited a hemolysis rate below 2%, indicating excellent in vitro antiangiogenic and antitumor activity as well as favorable blood compatibility. Additionally, both CRE and CREM demonstrated favorable tumor targeting capabilities through the specific binding action of cyclic RGD (cRGD) to integrin αvß3. Further in vivo investigations revealed that CREM induced apoptosis in tumor cells via the mitochondrial apoptotic pathway and reduced the expression of angiogenic factors such as vascular endothelial growth factor (VEGF), thereby inhibiting tumor angiogenesis. This potent antitumor effect was evident through a tumor suppression rate of 80.19%. Importantly, histopathological staining (HE staining) demonstrated the absence of significant toxic side effects of CREM on various organs compared to MTX. In conclusion, the CREM nano drug delivery system synergistically enhances the therapeutic efficacy of antiangiogenic drugs and chemotherapeutic agents, thus offering a novel targeted approach for cancer treatment.
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Quitosana , Metotrexato , Oligossacarídeos , Metotrexato/química , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Quitosana/química , Animais , Humanos , Camundongos , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Portadores de Fármacos/química , Linhagem Celular Tumoral , Nanopartículas/química , Proliferação de Células/efeitos dos fármacos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Integrina alfaVbeta3/metabolismo , Oligopeptídeos/química , Oligopeptídeos/farmacologiaRESUMO
In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Infusões Intra-Arteriais , Neoplasias Hepáticas , Humanos , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Terapia Combinada , Artéria Hepática , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/terapia , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. RESULTS: The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. CONCLUSION: In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Artéria Hepática , Infusões Intra-Arteriais , Neoplasias Hepáticas , Humanos , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/terapia , Infusões Intra-Arteriais/métodos , Resultado do Tratamento , Terapia Combinada , Antineoplásicos/administração & dosagem , Feminino , MasculinoRESUMO
Introduction: Allium is important vegetables and seasonings in China, Tibet is rich in unique resources of the genus Allium, but lacks development and utilization. Methods: We compared the biological features and comprehensively evaluating the quality of twelve germplasm resources of the genus Allium collected from Tibet. Results: The results revealed that nine germplasm resources were bolting and bloom normally except for SC015, SC019, and SC048, all twelve germplasm resources were able to vegetative growth. The individual differences in moisture, soluble sugar, and protein content among the twelve germplasm resources were relatively small, with pyruvic acid content ranging from 0.11 to 1.12 mg/g and a large variation coefficient. A total of 8 categories and 97 volatile compounds were detected in twelve germplasm resources, the majority possessed the highest proportions of aldehydes and organosulfur compounds, but there were certain differences between the different Allium species. Additionally, 11 to 16 types of free amino acids were present in all germplasm resources, proline exhibited the highest content. The total content of essential and non-essential amino acids in SC009 was the highest. Carbon (C) accounted for the largest proportion of all elements, and the contents of other mineral elements varied greatly among the different plants. Conclusion: In conclusion, combined with biological performance and comprehensive evaluation of quality, SC009 is the excellent germplasm resource suitable for growth and capable of reproduction with good quality. These results improved the exploitation and utilization of the genus Allium in Tibet, as well as provided germplasm resources for high-quality breeding of the genus Allium.
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The outbreak of the coronavirus disease 2019 (COVID-19) pandemic threatened adolescents' mental health and livelihoods, which can worsen their non-suicidal self-injury (NSSI) behaviors. With the significant increase of total online time use, adolescents become more prone to problematic internet use (PIU). This study examined whether depression mediated the relationship between PIU and NSSI among adolescence during the COVID-19 outbreak. Constructed with a cross-sectional design during the COVID-19 outbreak in Taiwan, 1060 participants were drawn from junior high schools through stratified and cluster sampling, and completed a set of comprehensive surveys. The mediation model demonstrated a good fit to the data, GFI = .96, CFI = .97, NFI = .97, NNFI = .95, IFI = .97, and SRMR = .02. The overall fit of the mediational model was adequate. The path from PIU to depression, ß = .41, p < .001, and the path from depression to NSSI, ß = .40, p < .001, were both significant. Moreover, the effect of PIU to NSSI decreased from .23 (p < .001) to .05 (p = .099) when depression was incorporated into the analysis. Moreover, results in bootstrapping analysis displayed that the indirect effect (PIU on NSSI via depression) was statistically significant (p < .001) and the direct effect (PIU on NSSI) was statistically non-significant (p = .134). The full mediation model was confirmed. The findings of the structure equation modeling and bootstrap analysis showed that PIU significantly and positively predicted NSSI, and that depression fully mediated this relationship.
Assuntos
COVID-19 , Depressão , Transtorno de Adição à Internet , Comportamento Autodestrutivo , Humanos , Adolescente , Comportamento Autodestrutivo/epidemiologia , COVID-19/epidemiologia , COVID-19/psicologia , Masculino , Feminino , Depressão/epidemiologia , Estudos Transversais , Transtorno de Adição à Internet/epidemiologia , Taiwan/epidemiologia , Comportamento do AdolescenteRESUMO
Geopolymer foam concrete (GFC), an emerging thermal insulation material known for its environmentally friendly and low-carbon attributes, has gained prominence for its use in bolstering building energy efficiency. A critical challenge in GFC production is foam destabilization by the alkaline environment in which foam is supersaturated with salt. In this study, GFC was prepared by using triterpene saponin (TS), sodium dodecyl sulphate (SDS), and cetyltrimethylammonium bromide (CTAB) as blowing agents, with fly ash as the precursor and calcium carbide slag (CA) combined with Glauber's salt (GS, Na2SO4 ≥ 99%) as the activator. The effect of GFC on mechanical properties was analyzed by examining its fluidity, pore structure, dry density, and compressive strength. The results show that TS has a stable liquid film capable of adapting to the adverse effects of salt supersaturation and alkaline environments. TS is highly stable in the GFC matrix, and so the corresponding pore size is small, and the connectivity is low in the hardened GFC. In addition, the hydration products of GFC exhibit different morphologies depending on the surfactant used. TS has better water retention due to hydrogen bonding, which facilitates the hydration process.
RESUMO
SUMMARY: Recent methodology advances in computational signal deconvolution have enabled bulk transcriptome data analysis at a finer cell-type level. Through deconvolution, identifying cell-type-specific differentially expressed (csDE) genes is drawing increasing attention in clinical applications. However, researchers still face a number of difficulties in adopting csDE genes detection methods in practice, especially in their experimental design. Here we present cypress, the first experimental design and statistical power analysis tool in csDE genes identification. This tool can reliably model purified cell-type-specific (CTS) profiles, cell-type compositions, biological and technical variations, offering a high-fidelity simulator for bulk RNA-seq convolution and deconvolution. cypress conducts simulation and evaluates the impact of multiple influencing factors, by various statistical metrics, to help researchers optimize experimental design and conduct power analysis. AVAILABILITY AND IMPLEMENTATION: cypress is an open-source R/Bioconductor package at https://bioconductor.org/packages/cypress/.